Autophagy-dependent ferroptosis in infectious disease.

Autophagy is the initial defense response of the host against pathogens. Autophagy can be either non-selective or selective. It selectively targets the degradation of autophagic substrates through the sorting and transportation of autophagic receptor proteins. However, excessive autophagy activity will trigger cell death especially ferroptosis, which was characterized by the accumulation of lipid peroxide and free iron. Several certain types of selective autophagy degrade antioxidant systems and ferritin. Here, we summarized the latest researches of autophagy in infection and discuss the regulatory mechanisms and signaling pathways of autophagy-dependent ferroptosis.

Effects of different antioxidants combined with high hydrostatic pressure on the color and anthocyanin retention of a blueberry juice blend during storage.

Blueberry juice has been found to undergo severe browning after treatment and cold storage, such as processing by high hydrostatic pressure (HHP) at 550 MPa/10 min/25 °C followed storage at 4 °C for 4 days. This browning may be due to the degradation of anthocyanin (AC) in the berries. Therefore, in this study, gallic acid (GA), ferulic acid (FA), ascorbic acid (VC), citric acid (CA), tea polyphenol (TP) and α-tocopherol (VE) were compared to determine their ability to improve the stability of the AC in HHP-treated blueberry juice. The juice was combined with the six abovementioned antioxidants at different concentrations, then treated by HHP at 550 MPa/10 min/25 °C and stored at 4 °C for 20 days. Thereafter, the pH levels, degrees °Brix, color parameters, total AC content and polyphenol oxidase (PPO) activity of the blueberry juice blend were measured and compared. Gallic acid at 2 g/L was found to be the most effective antioxidant to protect against AC degradation. After storage at 4 °C for 20 days, the AC content of the juice with no added antioxidants had decreased by 62.27% with a PPO relative activity of 50.78%, while the AC content of juice supplemented with 2 g/L GA had decreased by 13.42% with a PPO relative activity of 28.13%. The results of this study, thus, suggest that GA can stabilize the structure of AC in blueberry juice and reduce PPO activity, which may be beneficial in guiding the production of blueberry juice with high AC retention.

Cardioprotective effect of ultrasound-targeted destruction of Sirt3-loaded cationic microbubbles in a large animal model of pathological cardiac hypertrophy.

Pathological cardiac hypertrophy occurs in response to numerous increased afterload stimuli and precedes irreversible heart failure (HF). Therefore, therapies that ameliorate pathological cardiac hypertrophy are urgently required. Sirtuin 3 (Sirt3) is a main member of histone deacetylase class III and is a crucial anti-oxidative stress agent. Therapeutically enhancing the Sirt3 transfection efficiency in the heart would broaden the potential clinical application of Sirt3. Ultrasound-targeted microbubble destruction (UTMD) is a prospective, noninvasive, repeatable, and targeted gene delivery technique. In the present study, we explored the potential and safety of UTMD as a delivery tool for Sirt3 in hypertrophic heart tissues using adult male Bama miniature pigs. Pigs were subjected to ear vein delivery of human Sirt3 together with UTMD of cationic microbubbles (CMBs). Fluorescence imaging, western blotting, and quantitative real-time PCR revealed that the targeted destruction of ultrasonic CMBs in cardiac tissues greatly boosted Sirt3 delivery. Overexpression of Sirt3 ameliorated oxidative stress and partially improved the diastolic function and prevented the apoptosis and profibrotic response. Lastly, our data revealed that Sirt3 may regulate the potential transcription of catalase and MnSOD through Foxo3a. Combining the advantages of ultrasound CMBs with preclinical hypertrophy large animal models for gene delivery, we established a classical hypertrophy model as well as a strategy for the targeted delivery of genes to hypertrophic heart tissues. Since oxidative stress, fibrosis and apoptosis are indispensable in the evolution of cardiac hypertrophy and heart failure, our findings suggest that Sirt3 is a promising therapeutic option for these diseases. STATEMENT OF SIGNIFICANCE: Pathological cardiac hypertrophy is a central prepathology of heart failure and is seen to eventually precede it. Feasible targets that may prevent or reverse disease progression are scarce and urgently needed. In this study, we developed surface-filled lipid octafluoropropane gas core cationic microbubbles that could target the release of human Sirt3 reactivating the endogenous Sirt3 in hypertrophic hearts and protect against oxidative stress in a pig model of cardiac hypertrophy induced by aortic banding. Sirt3-CMBs may enhance cardiac diastolic function and ameliorate fibrosis and apoptosis. Our work provides a classical cationic lipid-based, UTMD-mediated Sirt3 delivery system for the treatment of Sirt3 in patients with established cardiac hypertrophy, as well as a promising therapeutic target to combat pathological cardiac hypertrophy.

Effects of Partial Replacement of NaCl with KCl on Protein Properties and Quality Attributes of Lightly Salted Tilapias Fillets.

The evolution of quality attributes and their association with the protein properties of lightly tilapias fillets salted with different replacement proportions of NaCl with KCl (0%, 10%, 30%, 50%, 70%, 100%) at the same ionic strength were investigated. KCl replacements using optimal substitution (50% of KCl) contributed to maintaining desired quality properties. Further, KCl replacement (about 50~70% of KCl) led to the insolubilization and weakened stability of myofibrillar proteins, represented by the unfolding of the myofibrillar protein, increased surface hydrophilic points, and strengthened internal protein-protein interaction, resulting in the structurally reinforced hardness and lower water-holding capacity. Excessive replacement (more than 70% of KCl) showed apparent deterioration in taste quality, coloration, and hardness received by sensory sensation caused by immoderate hydrolysis and aggravated oxidation of the myofibrillar protein. In this sense, insights into KCl replacements on protein properties might be a positive approach to improving quality attributes of lightly salted tilapias fillets.

Dexmedetomidine alleviates renal tubular ferroptosis in sepsis-associated AKI by KEAP1 regulating the degradation of GPX4.

Sepsis-associated acute kidney injury (SA-AKI) has a high mortality rate and lacks effective targeted treatment. We applied lipopolysaccharides-induced injury models in human and mouse renal tubular epithelial cells, and at the same time, we selected a commonly used sedative drug, dexmedetomidine, to investigate its potential for renal protection. We found a significant increase in the expression level of HSP90, and the interaction with glutathione peroxidase 4 (GPX4) led to autophagic degradation of GPX4, triggering ferroptosis. Dexmedetomidine reduced the degradation of GPX4 by increasing the binding of KEAP1 and HSP90 in the cytoplasm. Therefore, lipid peroxidation and ferroptosis were reduced. Similarly, dexmedetomidine showed renal protective effects in C57BL/6J male mice with SA-AKI induced by cecal ligation. Our study reveals a new mechanism of renal tubular epithelial cell ferroptosis in SA-AKI treated with dexmedetomidine.

[Kelch-like ech-associated protein 1/nuclear factor E2-related factor 2/antioxidant response element pathway alleviates ferroptosis in sepsis by regulating oxidative stress].

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, and has a high morbidity and mortality worldwide. The characteristic of sepsis is the inflammatory reaction. Cytokines produced by the severe inflammatory reaction can activate neutrophils and cause excessive production of reactive oxygen species (ROS), thus damage cells and tissue, and further develop into organ dysfunction and failure. Ferroptosis is an iron-dependent form of nonapoptotic cell death discovered recently. Its main mechanism is the intracellular lipid peroxidation induced by iron and the low expression of antioxidant systems [glutathione (GSH) and glutathione peroxidase 4 (GPX4)]. Recently, many studies have shown that Kelch-like ech-associated protein 1/nuclear factor E2-related factor 2/antioxidant response element (Keap1/Nrf2/ARE) signal pathway can improve oxidative stress and alleviate ferroptosis in sepsis. This article reviews the molecular mechanism and research of Nrf2 inhibiting ferroptosis in sepsis, in order to innovate prevention and treatments for the intervention of sepsis.